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The biphasic effect of extracellular glucose concentration on carbachol‐induced fluid secretion from mouse submandibular glands
Author(s) -
Terachi Momomi,
Hirono Chikara,
Kitagawa Michinori,
Sugita Makoto
Publication year - 2018
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12417
Subject(s) - extracellular , medicine , carbachol , endocrinology , secretion , submandibular gland , phlorizin , chemistry , extracellular fluid , cholinergic , biology , glucose transporter , insulin , biochemistry , receptor
Cholinergic agonists evoke elevations of the cytoplasmic free‐calcium concentration ([Ca 2+ ] i ) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh‐induced fluid secretion. The CCh‐induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium–glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1‐mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl − secretion in real‐time. High extracellular glucose levels may suppress the CCh‐induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca 2+ ] i signals.